This proposal requests continued NIA funding for the Midcareer Investigator Award in Patient-Oriented Research (K24) to Mark W. Bondi, PhD. During the first 5 years of support provided by the K24 award, Dr. Bondi has upgraded his own skill set as a research mentor by completing focused training with arterial spin labeling (ASL) and diffusion tensor imaging (DTI) MRI techniques and implementing them in his research lab with his trainees. During this period, he has obtained four patient-oriented research grants (R01, R43, and R44 grants from the NIA and an Investigator-Initiated Research Grant from the Alzheimer's Association). He has also served as primary mentor or co-mentor to 12 clinician-scientists in training. Eight of these trainees have gone on to receive either mentored or independent research support, or both, from NIH (4 NRSA; 1 SC3), the Dept of Veterans Affairs (4 VA Career Development Awards), the Dept of Defense (2 Investigator-Initiated Grants), and private foundations (3 New Investigator Research Grants from the Alzheimer's Association; 1 New Investigator Grant from AFAR). Furthermore, all of the mentees have published one or more first- authored peer-reviewed research papers reporting their work (40 unique mentee publications since 2007), and eight trainees from his lab now work in full-time academic patient-oriented faculty or research positions. The need for training and support of nascent patient-oriented researchers is both acute and profound. UCSD and the VASDHS are fortunate to have several formal training programs (including departmental T32 training grants and VA post-doctoral fellowship programs) to support the structured didactic training of clinician- scientists. Each of these programs requires the availability of skilled mentors. The K24 award permits Dr. Bondi, an established and productive clinician scientist whose integrative work in neuropsychology and neuroimaging has helped to shape our understanding of the prodromal period of Alzheimer's disease (AD), to devote substantial time to mentoring new patient-oriented researchers. It also provides him with time to enhance his own research skills in order to mentor new clinical investigators and to conduct meritorious patient-oriented research. This proposed one-time opportunity for 5 years of continued support will focus on facilitating the convergence of his research group's expertise in neuropsychology and neuroimaging studies with their growing skill and interest in the utilization of biomarkers in support of characterizing the prodromal period of dementia. With the help of several identified 'resource' experts in advanced neuroimaging and CSF biomarker techniques, Dr. Bondi proposes to enrich and deepen his research expertise in these areas with the dual aims of (1) maintaining his group's efforts at the vanguard of early detection research, and (2) simultaneously transmitting these skills to the clinician scientists he mentors in an effort to advance their own careers in patient-oriented research in early detection, diagnosis and clinical outcomes in dementia. PUBLIC HEALTH RELEVANCE: We are entering a new era of research and clinical activity that will increasingly focus on the role of biomarkers in dementia detection, diagnosis, and clinical outcome. Critical empirical appraisals of these multi-modal techniques will be needed, and the research aims of this project will seek to integrate cognitive, imaging, and other biomarker methods that best characterize the development of dementia. Through the project's training aims, the candidate will also play a major role in contributing to the career development of young investigators who will work in this interdisciplinary field as the next generation of patient-oriented researchers.